Sellke F W, Wang S Y, Stamler A, Lopez J J, Li J, Li J, Simons M
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):H713-20. doi: 10.1152/ajpheart.1996.271.2.H713.
Changes in the vascular responses to vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in chronically ischemic myocardium have not been investigated. Ameroid constrictors were placed on the proximal left circumflex (LCX) artery of seven Yorkshire pigs. Seven to nine weeks later, myocardial blood flow in the collateral-dependent LCX region was reduced, compared with that in the normally perfused left anterior descending (LAD) region. Both growth factors elicited significant relaxations of coronary microvessels. Relaxations to both VEGF and bFGF were inhibited in the presence of either NG-nitro-L-arginine or genistein, suggesting that the relaxations are through the tyrosine kinase-mediated release of endothelium-derived nitric oxide. Microvascular relaxations to both VEGF or bFGF were significantly greater in vessels harvested from the collateral-perfused LCX region, compared with those taken from the normally perfused LAD region. However, relaxation to the endothelium-dependent vasodilator ADP, which does not operate through a tyrosine kinase receptor, was reduced in the collateral-perfused region, compared with the normally perfused territory, suggesting a possible link of tyrosine kinase to the enhanced relaxations to VEGF and bFGF in collateral-perfused coronary microvessels. Northern analysis showed increased expression for both VEGF receptors (flk-1, flt-1) as well as the bFGF receptor 1 (FGFR-1) in the collateral-perfused region compared with that in the normally perfused region. This suggests that the increased relaxation responses to VEGF and bFGF in the ischemic myocardium may be related to increased gene expression of the respective tyrosine kinase receptors.
慢性缺血心肌中血管对血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的反应变化尚未得到研究。在7只约克夏猪的左回旋支（LCX）近端放置Ameroid缩窄环。7至9周后，与正常灌注的左前降支（LAD）区域相比，侧支循环依赖的LCX区域心肌血流量减少。两种生长因子均可引起冠状动脉微血管的显著舒张。在存在NG-硝基-L-精氨酸或染料木黄酮的情况下，对VEGF和bFGF的舒张作用均受到抑制，这表明舒张作用是通过酪氨酸激酶介导的内皮源性一氧化氮释放实现的。与从正常灌注的LAD区域采集的血管相比，从侧支循环灌注的LCX区域采集的血管对VEGF或bFGF的微血管舒张作用明显更强。然而，与正常灌注区域相比，侧支循环灌注区域对不通过酪氨酸激酶受体起作用的内皮依赖性血管舒张剂ADP的舒张反应降低，这表明酪氨酸激酶可能与侧支循环灌注的冠状动脉微血管对VEGF和bFGF增强的舒张反应存在联系。Northern分析显示，与正常灌注区域相比，侧支循环灌注区域中VEGF受体（flk-1、flt-1）以及bFGF受体1（FGFR-1）的表达增加。这表明缺血心肌中对VEGF和bFGF增强的舒张反应可能与相应酪氨酸激酶受体的基因表达增加有关。
